Jaundice of the newborn results from the accumulation of bilirubin in blood. Elevations in the serum level of this end product of heme degradation occur because of delays in the normal postnatal development increase in bilirubin uridinediphospho (UDP)-glucuronosyltransferase activity. This enzyme converts unconjugated bilirubin to bilirubin monoglucuronide and bilirubin diglucuronide which are excreted into bile and eliminated from the body. Treatment of jaundiced newborns is a major concern of pediatricians because bilirubin can enter neural tissues resulting in central nervous system toxicity. Thus, jaundice continues to be a common cause of prolonged hospitalization in newborns.
Phototherapy is the generally recommended form of treatment if bilirubin concentration reaches 14-15 mg/dl. An exchange transfusion is the generally recommended form of treatment if bilirubin concentration reaches levels of 20 mg/dl. These are complicated procedures and add to the expense of health care.
Phenobarbital has been administered to cause reduction of levels of serum bilirubin in newborns. Phenobarbital has been determined to function in this treatment by increasing the expression of the bilirubin/phenol UDP-glucuronosyltransferase ugt1 gene to cause increased levels of bilirubin UDP-glucuronosyltransferase activity. While this treatment increases the metabolism of bilirubin by upregulating the enzyme that is deficient in newborns, phenobarbital is not routinely used in the treatment of newborn jaundice because of its side effects, namely that it is habit-forming, causes drowsiness, can cause withdrawal problems and may be a cancer causer and/or promoter.
Recently, the Wall street Journal published an article about treating newborn jaundice by administering protoporphyrins, e.g., tin protoporphyrin. This treatment appears to be addressed in U.S. Pat. Nos. 4,831,024 and 5,081,115. The protoporphyrins function by inhibiting the breakdown of heme but do not cause an increase in bilirubin UDP-glucuronosyltransferase activity, i.e., upregulate the enzyme that is deficient in newborns.